Thrombin-Mediated Degradation of Human Cardiac Troponin T

Katrukha, Ivan A; Коган, А. Х.; Vylegzhanina, Alexandra V; Serebryakova, Marina V.; Koshkina, Ekaterina V.; Bereznikova, A.; Katrukha, Alexey G.

doi:10.1373/clinchem.2016.266635

Cited by 64 publications

(47 citation statements)

References 33 publications

(44 reference statements)

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“… 92 This is primarily due to the fact that different anti-hs-TnI antibodies directed to different antigenic determinants of the cTnI molecule are used in different kits. In accordance with recent research results, it has been established that cTnI and cTnT fragments that have different stability 94 , 95 differ in resistance to various proteolytic enzymes 96 , 97 and in elimination abilities, 48 , 74 , 76 circulate in the blood to a greater extent in AMI. For example, when using antibodies directed against unstable epitopes or fragments of cTnI and cTnT, the results of the test may be underestimated in comparison with those obtained using test kits with anti-cTnI and anti-cTnT antibodies against more stable fragments or areas of cardiac troponin molecule.…”

Section: Some New Data On Troponin Biochemistry and Diagnostic Capabilities Of High-sensitivity Troponin Assayssupporting

confidence: 85%

Cardiac Troponins: Contemporary Biological Data and New Methods of Determination

Chaulin¹

2021

VHRM

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Laboratory diagnosis plays one of the key roles in the diagnosis of many diseases, including cardiovascular diseases (CVD). The methods underlying the in vitro study of many CVD biomarkers, including cardiac troponins (cTnI and cTnT), are imperfect and are continually being improved to enhance their analytical performance, with sensitivity and specificity being the most important. Recently developed improved cTnI and cTnT detection methods, referred to as highly sensitive methods (hs-cTnI, hs-cTnT), have changed many of our ideas about the biology of cardiac troponins and opened up a number of additional diagnostic capabilities for practical healthcare. This article systematizes some relevant data on the biology of cardiac troponins as well as on methods for determining cTnI and cTnT with an analysis of the diagnostic value of their analytical characteristics (limit of blank, limit of detection, 99th percentile, coefficient of variation, and others). Data on extracardiac expression of cTnI and cTnT, mechanisms of formation and potential clinical significance of gender, age, and circadian characteristics of hs-cTnI and hs-cTnT content in serum are discussed. Considerable attention is paid to the discussion of new diagnostic capabilities of hs-cTnI, hs-cTnT, including consideration of promising possibilities for their study in biological fluids that can be obtained by non-invasive methods. Also, some possibilities of using hs-cTnI and hs-cTnT as prognostic laboratory biomarkers in healthy people (for example, to assess the risk of developing CVD) and in patients suffering from a number of pathological conditions that cause damage to cardiomyocytes are examined, and the potential mechanisms underlying the increase in hs-cTnI and hs-cTnT are discussed.

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Section: Some New Data On Troponin Biochemistry and Diagnostic Capabilities Of High-sensitivity Troponin Assayssupporting

confidence: 85%

Cardiac Troponins: Contemporary Biological Data and New Methods of Determination

Chaulin¹

2021

VHRM

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“…serum for Roche hs-cTn T and heparin plasma for Abbott hs-cTn I) may be therefore noticeable and should require appropriate assay (re)validation and, more importantly, the redefinition of clinical thresholds specific for each employed sample. Incidentally, Katrukha et al, using a proteomic analysis, showed a consistent difference in the composition of cTn T forms in simultaneously collected serum and heparin plasma samples from the same patients with AMI [54]. While heparin plasma samples contained full-sized cTn T (~35 kDa), in serum samples cTn T was present in a 29-kDa form as a probable result of thrombin-mediated cleavage of cTn T molecule occurring in vitro during the clotting process.…”

Section: Understanding the Impact Of Pre-analytical And Analytical Inmentioning

confidence: 98%

Laboratory-related issues in the measurement of cardiac troponins with highly sensitive assays

Krintus

Panteghini

2020

Clinical Chemistry and Laboratory Medicine (CCLM)

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A number of assay-related issues can affect the performance of cardiac troponin (cTn) measurement in everyday practice. In this respect, it is vital that all information on cTn assays is known and that the performance characteristics of assays are objectively assessed and adequately described. The advent of the latest generation of more sensitive cTn assays has heralded a new wave of information about low concentrations of cTn in blood. These recent generation assays have improved analytical sensitivity and corresponding performance at low cTn concentrations when compared to their predecessors, providing a convincing goal for laboratory medicine in helping clinicians in the diagnosis of acute myocardial infarction. Crucial to the clinical utility of highly sensitive cTn assays is the laboratorians’ role in closely scrutinizing proposed assays and defining their value in relation to available evidence. Analytical, as well as pre-analytical and post-analytical, aspects must be documented. In this review, we describe what laboratory professionals should know about their cTn assay performance characteristics and the pre-analytical prerequisites for robustness to ensure optimal post-analytical reporting.

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“…Недавно было обнаружено, что тропонины могут специфически расщепляться ферментом тромбином непосредственно в кровотоке. Добавление специфического ингибитора тромбина не приводило к расщеплению тропонина Т [28]. Стоит предположить участие многих других протеолитических ферментов, в том числе и ферментов системы гемостаза в процессах внеклеточного разрушения тропонинов, что нуждается в дальнейшем изучении.…”

Section: Introductionunclassified

Cardial Troponins Metabolism Under Normal and Pathological Conditions

Chaulin¹,

Dispensary²,

Karslyan³

et al. 2019

SMR

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Самарский областной клинический кардиологический диспансер, Самара 443070, Российская Федерация 2 Самарский государственный медицинский университет, Самара 443099, Российская Федерация Резюме. В обзорной статье представлены современные представления об особенностях метаболизма тропониновых белков, которые оказывают влияние на результаты анализов. Большое внимание уделено механизмам высвобождения тропонинов из здоровых и поврежденных по различным причинам кардиомиоцитов. Приводятся актуальные сведения, касающиеся протеолитической деградации тропонинов внутри клетки и кровотоке, которые определяют различия между результатами тропониновых диагностикумов. Сообщается о недавно проведенных исследованиях, посвященных неинвазивному определению тропонинов в моче и ротовой жидкости. Обсуждается значение и возможные причины циркадных колебаний концентрации кардиального тропонина Т по данным высокочувствительного определения. Ключевые слова: обзор литературы, лабораторная диагностика, сердечные тропонины, инфаркт миокарда, высвобождение и элиминация тропонинов, апоптоз кардиомиоцитов, циркадные колебания, метаболизм. Конфликт интересов. Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.

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Thrombin-Mediated Degradation of Human Cardiac Troponin T

Abstract: The results of this study suggest that the 29-kDa fragment of cTnT in AMI serum samples mainly appears due to the cleavage by thrombin during serum sample preparation.

Cited by 64 publications

References 33 publications

Cardiac Troponins: Contemporary Biological Data and New Methods of Determination

Cardiac Troponins: Contemporary Biological Data and New Methods of Determination

Laboratory-related issues in the measurement of cardiac troponins with highly sensitive assays

Cardial Troponins Metabolism Under Normal and Pathological Conditions

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